Several types of studies suggest a partial overlap between the neural mechanisms mediating drug reward and those mediating food reward. This overlap holds forth the intriguing possibility that dietary manipulations may be useful as adjuncts to approaches for prevention and treatment of drug abuse. Currently, there is a lack of information about the influence of dietary factors on two processes that are thought to be important factors in drug abuse: sensitization and relapse. The animal studies described in this proposal will address these issues. Experiments in Part 1 will determine whether intermittent pre-exposure to sucrose will produce or facilitate sensitization to the locomotor activating effects of cocaine. To this end, rats will be given 1 of 3 different schedules of pre-exposure to sucrose, and the response to an initial and to repeated injections of cocaine will be measured. Experiments in Part 2 will examine whether intermittent pre-exposure to sucrose will produce sensitization to the reinforcing effects of cocaine, as measured by differences in the rate of acquisition and dose-response relationships in the intravenous self-administration model. Experiments in Part 3 will examine whether brief exposure to sucrose will cause a reinstatement to cocaine seeking in rats that have undergone extinction of self-administration behavior. The effect of sucrose on reinstatement caused by priming infusions of cocaine will also be examined. It is hypothesized that pre-exposure to sucrose will, under some conditions, produce a sensitization to the locomotor and/or reinforcing effects of cocaine. It also is hypothesized that sucrose intake will cause some degree of reinstatement of drug seeking, and that the presence of this palatable food will influence the effect of a priming infusion on drug seeking. To determine the food-specificity of any observed effects, follow-up experiments will be conducted with pre-exposure to dietary fat. An investigation of the impact of dietary factors on the processes of sensitization and reinstatement will provide a better understanding of the contribution of disordered eating patterns to the initiation, maintenance or relapse to human drug abuse. Ultimately, improved nutritional counseling and/or manipulations of dietary factors may be helpful in efforts to prevent or treat drug abuse.
| Thompson, A M; Swant, J; Gosnell, B A et al. (2004) Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration. Neuroscience 127:177-85 |
